Gamma-morpholinopropyl cinnamate salt of penicillin



Patented Oct. 6, 1953 GAMllIA-MORPHOLINOPROPYL CINNAMATE SALT OF PENICILLIN Harley W. Rhodehamel, Jr., Indianapolis, Ind., assignor to Eli Lilly and Company, Indianapolis, Ind., a corporation of Indiana N Drawing. Application February 13, 1952, Serial No. 271,432

2 Claims. (Cl. 260239.1)

This invention relates to a novel penicillin mixture is cooled and stirred occasionally wheresalt and the preparation thereof. upon the slightly soluble 'y-morpholinopropyl I have discovered that -morpholinopropyl cinnamate salt of penicillin G precipitates. The cinnamate or its salts can be combined with penisalt is separat n dri d n va u cillin or its salts by neutralization or metatheti- 5 'y-Morpholinopropyl cinnamate can be precal reactions to form a sparingly soluble penipared by esterification of cinnamic acid with cillin salt, thereby affording a means of precipiv-m p in p op nol y th usual methods.

tating penicillin from solution, and of purifying Acid addition salts of 'y-m p p pyl cinpenicillin. Moreover, the novel penicillin salt namate are a y p p d y the interreaction lean be utilized therapeutically. A prolonged of equivalent amounts of the base and the depenicillin blood level can be secured upon adsired acid in inert solvent solution, followed y ministering the salt parenterally by methods removal f the solventknown to the medical art. I clam:

The following examples illustrate the prepara- 'P F 'l'morphollnopropyl Cmnamate salt of tion of the novel salt f this invention; penicillm represented by the following formula in which P represents penicillin: Example 1 To 3 g of a solution of penicillin (e g a com CHPCH: mercial mixture of the several penicillins) dis- Y solved in 50 ml. of amyl acetate are added 3 g. O P CHPCH' of 'y-morpholinopropyl cinnamate dissolved in ml. of amyl acetate. The mixture is cooled and The stirred occasionally whereupon the -morphopenicillin p mopropyl cmnamate Salt of linopropyl cinnamate salt of penicillin precipi- HARLEY W, RHODEHAMEL, Jr. tates. The salt is isolated as by decantation or 25 filtration and dried vacuo References in the file Of patent The salt is represented by the following for- UN T STATES PATENTS mula m which P represents penicillin. Number N am e D at e 2,515,898 Rhodehamel July 18, 1950 CH=CHOCH2C:H2CH2- /O O P CHPGH' Number Country Date 659,775 Great Britain Oct. 24, 1951 Emmple 2 35 OTHER REFERENCES To an aqueous solution of 0.3 g. of the potas- Ballaro: "Ciencia e Investigacion, vol. 4, Nosium salt of penicillin G in 1.8 ml. 01 water is vember 1948, pp. 481, 482. added a solution of 0.3 g. of -morpholinopropyl Rhodehamel: J. Am. Chem. Soc, vol. 73,

cinnamate hydrochloride in 5 ml. of water. The December 1951, p. 5902, 

1. THE Y-MORPHOLINOPROPYL CINNAMATE SALT OF PENICILLIN REPRESENTED BY THE FOLLOWING FORMULA IN WHICH P REPRESENTS PENICILLIN: 